Sulphones and process of preparing same



- lowing general formula Patented Nov. 20. 1945 UNITED STATES PATENT OFFlCE SULPHONES AND PROCESS OF PREPARING SAME Louis L. Bamlias, Grosse Pointe Woods, Mich, as-

signor to Parke, Davis & Company, Detroit, Mich, a corporation of Michigan No Drawing. Application June 13, 1944,

- Serial No. 540,136

The compounds of the invention have the folwhere-Z and Z are members of the class consisting of N02, NH: and groups hydrolyzable to NH:;, An important compound within the general class is 2,4-diamino--(1,3,4-thiodiazolyl) phenyl sulphone which has been found to be a chemotherapeutic agent of outstanding utility in the treatment of bacterial infections.

The following examples illustrate methods for the preparation of the new class of compounds as well as for certain intermediates.

Example 1.Preparation of 2-amino-4'-nitro-5- thiodiazolyl-phenyl sulphide Thio-semicarbazide may be prepared by the method of Freund & Schander, Ber. 29 2501 (1896). It may be converted into 2-amino-5- thio-thiodiazole by the method '01 P. C. Guha, J. A. C. S. 44 1516 (1922).

600 grams of 2-amino-E-thio-thiodiazole is dissolved in 1 liter of water with sufllcient alkali and 5 liters of 3-A ethanol are added. 600 grams of p-nitro chlorobenz ene is added and the solution refluxed for 40 hours. The solution is cooled and the crystals filtered. The filter cake is suspended in ether to free of p-nitro chlorobenzene and filtered. The filter cake is 2-amino-4'-nitro- B-thiodiazolylphenyl sulphide, having a melting point of 196200 C. The equation for this reaction is as follows:

, N. NO,C C1+NaS( yl-NHi e i i NOOSG- VC--NH:

Example 2.--Preparaticm of 2-acetuZamino-4'- nitro-s-thiodiazolylphenyl sulphone 700 grams of the product obtained in Example 1 is suspended in a solution of 1.7 liters of acetic anhydride in 6 liters of glacial acetic acid, 1750 cc. of 30% hydrogen peroxide is added portionwise with the temperature rising to Bil- C..

Cooling is instituted to keep the temperature at 80-90 C. When the temperature drop .more H202 is added, the suspension goes into solution and then is recrystallized as formed. After the reaction is complete, the reaction mixture is allowed to stand at 80-90 C. for 2 hours, then cooled and filtered. The product thus obtained is 2-acetylamino-4'-nitro-5-thiodiazolyl phenyl sulphone of melting point 250-254 C. and has the formula l O K Example 3.-Preparation of 2-amtno-4'-nitro-5- thiodiazolylpheayl sulphone The product of Example 2 may be deacetylated by suspending 620 grams in a solution of 4.5 liters of glacial acetic acid, 500 cc. of hydrochloric acid and 500 cc. of water. The mixture is refluxed until complete solution and then 30 minutes longer. The solution is cooled, neutralized t0 Congo red with dilute alkali and diluted further to precipitate crystalline v2-amino-4'-nitro-5- thiodiazolylphenyl sulphone of melting point 228-232 C.

Example 4.Preparation of 2, 1'-diamino-5- thiodz'azolylphenyl sulphone grams of ammonium chloride is dissolved in 10 liters of hot water and 600 grams of resupernatant liquid is decanted off. The sludge is made alkaline to litmus with alkali and then extracted with an equal volume of hot acetone.

The acetone solution is filtered off. The filtrate is reduced in vacuo until all acetone is taken oil. The residue is cooled and the pinkish-yellow or flesh-colored crystals are filtered off and dried. when recrystallized from dilute alcohol orother suitable solvent, a product is obtained having a melting point 233-236 C. which is 2,4'-diamino- S-thio-diazolylphenol sulphone.

Example 5.Preparation of 2.4'-diaculated diamino-5-thiodiazolulphenyl sulphone The product of Example 4- may be diacetylated with acetic anhydride according to known methods for acetylation. Other equivalent acylating agents may also be used thereby obtaining the corresponding compounds in which the amino groups are replaced by groups which are hydrolyzable to amino groups.

What I claim as my invention is:

1. In a process for preparing a sulphone having the formula .where Z and Z' are members of the class consisting of N02, NH: and groups hydrolyzable to NH:, the step which comprises reacting a compound of the formula with a compound or the formula smears? 5 where M is a member of the class consisting of hydrogen and an alkali metal thereby obtaining a compound having the formula.

and oxidizing the latter with a reagent capable of converting the sulphide into a sulphone.

2. In a process for obtaining a sulphone, the step of reacting a p-nitro phenyl halide with a 2-amino-5-thio-thiodiazole thereby obtaining 2-amino-4'-nitro-5-thiodiazolylphenyl sulphide.

3. In a process for obtaining a sulphone, the

step of reacting a p-nitro phenyl halide with a 2-amino-5-thio-thiodiazole thereby obtaining 2-amino-4'-nitro-5-thiodiazolylphenyl sulphide, and oxidizing the latter with a reagent capable of converting a sulphide to a sulphone. 4. The process for manufacturing 2,4'-diamino-5-thiodiazolylphenyl sulphone which comprises reacting a p-nitro Dhenyi halide with a 2-amino-5-thio-thiodiazoie, oxidizing the 2-amino-4'-nitro-5-thiodiazo1ylphenyl sulphide thus obtained in the presence of an acylating agent to 2-acylamino-4' nitro-5-thiodiazoly1- phenyl sulphone, and deacylating and reducing to obtain 2,4-diamino-5-thiodiazolylphenyl sul phone. as 5. A compound having the formula where Z and Z are members of the class consisting of N02, NH: and groups hydrolyzable 

